(2012) - Methodology of Photic Stimulation Revisited Updated European Algorithm For Visual Stimulation in The EEG Laboratory

Epilepsia, 53(1):16–24, 2012
doi: 10.1111/j.1528-1167.2011.03319.x
CRITICAL REVIEW AND INVITED COMMENTARY
Methodology of photic stimulation revisited: Updated

European algorithm for visual stimulation in the
EEG laboratory
*Dorothée Kasteleijn-Nolst Trenité, yGuido Rubboli, zEdouard Hirsch, xAntonio Martins da
Silva, {Stefano Seri, #Arnold Wilkins, **Jaime Parra, yyAthanasios Covanis, zzMaurizio Elia,
xxGiuseppe Capovilla, {{Ulrich Stephani, and ##Graham Harding
*Department of Neuroscience, University Sapienza, Rome, Italy; yNeurology Unit, IRCCS Institute of Neurological Sciences,
Bologna, Italy; zDepartment of Neurology, Hopitaux Universitaires de Strasbourg, Strasbourg, France; xDepartment of
Neurological Disorders and Senses, Hospital Santo António, Oporto, Portugal; {School of Life and Health Sciences, Aston, University,
Birmingham, United Kingdom; #Visual Perception Unit, University of Essex, Colchester, United Kingdom; **Epilepsy Unit, Hospital
La Zarzuela, Madrid, Spain; yyNeurology Department, Agia Sophia Children’s Hospital, Athens, Greece; zzIRCCS Associazione Oasi
Maria SS, Troina, Italy; xxEpilepsy Center ‘‘C. Poma Hospital,’’ Child Neuropsychiatry Department, Mantova, Italy;
{{Neuropediatric Department, University of Kiel, Kiel, Germany; and ##Vision Sciences, Aston University,
Birmingham, United Kingdom
stantially increased content, detailing technical and logisti-

SUMMARY
cal aspects of IPS testing and the rationale for many of the
Intermittent photic stimulation (IPS) is a common proce- steps in the IPS procedure. Furthermore, our latest algo-
dure performed in the electroencephalography (EEG) lab- rithm incorporates the consensus of repeated scientific
oratory in children and adults to detect abnormal meetings of European experts in this field over a period of
epileptogenic sensitivity to flickering light (i.e., photosensi- 6 years with feedback from general neurologists and epi-
tivity). In practice, substantial variability in outcome is leptologists to improve its validity and utility. Accordingly,
anecdotally found due to the many different methods used our European group has provided herein updated algo-
per laboratory and country. We believe that standardiza- rithms for two different levels of methodology: (1) require-
tion of procedure, based on scientific and clinical data, ments for defining photosensitivity in patients and in family
should permit reproducible identification and quantifica- members of known photosensitive patients and (2)
tion of photosensitivity. We hope that the use of our new requirements for tailored studies in patients with a clear his-
algorithm will help in standardizing the IPS procedure, tory of visually induced seizures or complaints, and in those
which in turn may more clearly identify and assist monitor- already known to be photosensitive.
ing of patients with epilepsy and photosensitivity. Our algo- KEY WORDS: Standardization, Intermittent photic
rithm goes far beyond that published in 1999 (Epilepsia, stimulation, Photoparoxysmal response, Guidelines,
1999a, 40, 75; Neurophysiol Clin, 1999b, 29, 318): it has sub- European.
Why Photic Stimulation? (repeatedly) be gathered, for example, in diagnosing syn-

dromes (1) and monitoring of treatment (2):
Intermittent photic stimulation (IPS) is used as one of 1 Paroxysmal photosensitive responses (PPRs) occur in
the activating methods in electroencephalography (EEG) several epileptic syndromes with generalized and/or focal
recordings in the investigation of patients with suspected or seizures. Relating photosensitivity to definite epileptic
known epilepsy. Although photic stimulation is the provo- syndromes is possible, taking into account other signs and
cation technique that can most easily be standardized, great symptoms like myoclonia, absences, eyelid fluttering,
diversity in methodology has occurred. When performed in intellectual decline, and so on (Kasteleijn-Nolst Trenit
an efficient, standardized and safe way with attention to et al., 1987, 2001). Specific syndromes have been recog-
details, much valuable information for the patients can nized also, that is, idiopathic occipital photosensitive epi-
lepsy with PPRs confined to the occipital area or with
Accepted September 21, 2011; Early View publication November 16, 2011. secondarily generalization after occipital onset (Guerrini
Address correspondence to Dorothe Kasteleijn-Nolst Trenit, Via Vit-
torchiano 81, 00189 Roma, Italy. E-mail: dkasteleijn@planet.nl; Dorothee.
et al., 1995; Yalcin et al., 2000; Panayiotopoulos, 2002).
kasteleijn@uniroma1.it In 1994 Panayiotopoulos stressed the co-occurrence of
Wiley Periodicals, Inc. headache and visual symptoms in occipital epilepsies,
ª 2011 International League Against Epilepsy and later studies have confirmed that migraine can be a
16
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17
Methodology of Photic Stimulation Revisited
symptom of visually induced occipital epileptiform dis- of the effect of nonpharmacologic treatment (type of
charges (Parisi et al., 2007; Parisi, 2009). Especially in glasses; which covered eye is most effective).
families with both migraine and epilepsy, headache can
be the sole manifestation of an epileptic event or be the
remaining complaint after antiepileptic drug (AED) treat-
Proposed Methodology
ment (Piccioli et al., 2009). Another specific syndrome What one needs to know before starting any IPS
strongly connected with photosensitivity is Jeavons syn- procedure
drome (Viravan et al., 2011).
A. Get sufficient clinical information
2 Quantification of the response to IPS (upper and lower
flash frequency thresholds eliciting a PPR) and tailored For risk assessment one needs to know whether the
studies with pattern and TV testing can help in advising patient—between 10 and 20 years of age (age range of max-
lifestyle restraints (video games, disco lights, TV pro- imum sensitivity)—is drug naive (AEDs diminish risk of
grams, and so on) (Rubboli et al., 2004) and in choice and provocation of generalized tonic–clonic seizures, GTCS);
evaluation of treatment. Prescription of blue-colored had a short night sleep (increased of risk of PPRs); had sei-
glasses (Capovilla et al., 2006) are useful in a variety of zures provoked by TV, sunlight, or computers; or has a his-
clinical situations, for example, in pregnancy, to avoid tory of visually induced seizures in family members.
antiepileptic therapy or polytherapy. There are, however, Comment: Several general factors, known to be activat-
indications that the colors selected individually to reduce ing in generalized epilepsies, such as sleep deprivation,
visual discomfort may offer an effective alternative in alcohol abuse, and drug withdrawal, can influence the
patients who do not respond to blue lenses or who do not degree of photosensitivity (Scollo-Lavizzari & Scollo-
accept them (Wilkins et al., 1999). Lavizzari, 1974; Ambrosetto & Tassinari, 1987).
In addition, repeated quantification of the responses to Although we do not know exactly how great the risk for
IPS make it possible to evaluate the individual antiepilep- the individual patient will be, all the preceding factors have
tic effect of AEDs (and its change in dosages) and prevent been shown to increase the likelihood of occurrence of a
patients from possible AED-withdrawal seizures (Pavl- stronger reaction to visual stimulation with the potential risk
ović et al., 2011). of eliciting a tonic–clonic seizure.
Because the presence or absence of an epileptiform EEG The proposed methodology diminishes risk of provoked
response to visual stimulation has many implications for the seizures greatly, but with the above-mentioned information,
patient, we propose a photic stimulation method that gives technicians are better prepared to further reduce the risk.
the maximal information on susceptibility to visual stimuli
B. No special requirements are needed for the patient before
and is relatively safe when performed systematically with
arriving at the EEG department
attention to details.
Two different levels of methodology are advised: No special requirements are needed; do not stop any med-
The first level comprises requirements for defining photo- ication the day before the EEG is recorded. If the patient is
sensitivity in patients and in family members of known known to be visually sensitive (PPR or clinical history),
photosensitive patients. The purpose is to obtain an advise the patient to avoid long duration of (extreme) visual
answer as to whether the patient is photosensitive or not stimulation with lack of sleep, for example, night-long
(high sensitivity, low specificity). The procedure can also video gaming and discotheque dancing the night before.
be repeated in the same patient for evaluation of pharma- Comment: For diagnostic purposes, it is most informative
cologic treatment. If the patient is photosensitive under to register an EEG in a drug-naive state. However, when the
methodology 1, the patient can be invited at a later time patient is already on AEDs, changing the medication shortly
for a more extensive EEG (see methodology 2) to define before the EEG registration will create a withdrawal situa-
his/her sensitivity to various visual stimuli with a higher tion with increase of PPRs and risk of seizures.
level of precision. The protocol can be performed in the
C. Organize Informed Consent
same hospital or the patient can be referred to other cen-
ters that specialize in visual stimulation in patients with Consent is especially important when performing a sec-
epilepsy. ond-level EEG in patients with known photosensitivity.
The second level comprises requirements for tailored stud- Informed consent is necessary not only from the patients (or
ies in patients with a clear history of visually induced sei- legal representatives), but also from family members, who
zures or complaints, and in those already known to be will be present in the room during the IPS procedure.
photosensitive. The patient will be stimulated with a Comment: IPS is by nature a provocation method.
variety of visual stimuli in order to give a tailor-made Although the risk of evoking a seizure will be very small
estimate of the personal risks that are encountered in daily when the IPS procedure is performed with care and with
life by the various visual stimuli (TV screens, video determination of thresholds, unexpected findings can never-
games, striped patterns, and so on), as well as evaluation theless occur, whether causally related to the flashing lights
Epilepsia, 53(1):16–24, 2012

doi: 10.1111/j.1528-1167.2011.03319.x
18
D. Kasteleijn-Nolst Trenité et al.
or not. Small children can be stimulated while sitting on the If the patient is sitting (or standing with extra security
lap of the parent or with the parents sitting nearby. There- measures taken to prevent any possible harm), clinical
fore, the parent will receive high intensity flashing lights as signs like subtle myoclonic movements in limbs and face
well. An EEG laboratory has in any case rescue medication can be noticed during IPS. Simultaneous video images are
at hand, such as midazolam or diazepam, in the event that a helpful and mandatory for precise detection of clinical
seizure occurs. signs.
In order to get the patient to sleep and relaxed with a
D. Perform IPS at least 3 min after hyperventilation (HV) or
minimum of artifacts, routine EEG recordings usually are
before HV
done with the patient lying on a bed with eyes closed. How-
Comment: After HV patients usually become drowsy and ever, both HV and IPS with different eye conditions can be
more relaxed. In adults and adolescents this might lower more easily performed by patients, while sitting (or stand-
their anxiety for IPS. IPS at the end of the EEG and with HV ing); modern EEG technology helps reduce artifacts. For
at the beginning maximizes the chances of obtaining a spon- capturing self induction with hand waving and eyelid
taneous sleep recording, especially in children (Kaleyias movements, patients necessarily need to be in an upright
et al., 2006). position.
E. Perform IPS for the first time always while the patient is G. Record before the actual IPS procedure starts at least
awake after a normal night sleep. If this registration does not 2.5 min with eyes open and 2.5 min with eyes closed
reveal photosensitivity and the patient has a history of visu-
Comment: This is to enable discrimination between spon-
ally induced seizures or if the influence of night sleep depri-
taneous and IPS-evoked discharges and to detect fixation-
vation (NSD) is of importance (JME patients), IPS can be
off sensitivity (Panayiotopoulos,1998). If the alpha-rhythm
performed in the early morning after a scheduled partial
shows a lower amplitude and less spindling, then it will be
NSD. If possible, perform IPS near the time of the day in
more likely that the patient is photosensitive (Brazzo, 2010;
which the patient had his/her evoked seizures.
Kasteleijn-Nolst Trenit, 1989).
Comment: Although photosensitive patients are mostly
H. Use a lamp with circular reflector that delivers flashes
found in an epilepsy population, a PPR can be found unex-
with an intensity of at least 0.70 Joule. Use a viewing dis-
pectedly in patients with other neurologic diseases and dis-
tance of 30 cm
ease states (migraine, Parkinson, head trauma, alcohol or
drug withdrawal, dementia) or simply because of genetic Comment: To achieve a maximum level of sensitivity,
predisposition (Kasteleijn-Nolst Trenit et al., 2011). uniform stimulation of the whole retina is essential. This is
Most patients with a clear recent history of visually better achieved by round stimulators than oblong ones,
induced seizures and without AED treatment will show a because the visual angles of stimulation for the latter are dif-
PPR in a routine registration with standardized IPS. IPS dur- ferent (Harding & Jeavons, 1994). Grids should be avoided
ing sleep does provoke PPRs only in rapid eye movement to prevent combining pattern and light stimulation
sleep; sleep deprivation is the most provocative state (Scol- (Kasteleijn-Nolst Trenit et al., consensus 1999a,b), unless
lo-Lavizzari & Scollo-Lavizzari, 1974). no PPR is found and the patient has a consistent history of
JME patients are particularly likely to show a PPR in the TV- or video game–induced seizures, in which case pattern
early morning and even more pronounced after NSD might play a predominant role. The energy output conveyed
(Labate et al., 2007). Variations in daytime biologic by the stimulator must ideally be close to 1 Joule, as many
rhythms in photosensitivity do exist, however. patients will show sensitivity only with higher light intensity
(Specchio et al., 2010). The lamp at 30 cm from the nasion
F. Use dim room lighting, an upright position of the patient,
of the patient diminishes photomyoclonic responses and
and when a tailored study is performed also simultaneous
most importantly the patient’s face, and thus evoked clinical
video recording
signs, e.g., eyelid movements and eye deviations can be
Comment: During IPS the patient should be observed for observed.
detection of clinical signs for safety and diagnostic reasons,
I. Explain to the patient what procedure will be followed
to help discover artifacts and notice change in eye condi-
and what precautions will be taken to prevent a seizure.
tions. At least dim room lighting is necessary to be able to
see the subtle clinical manifestations, that often accompany Comment: Flashing lights of high luminance are poten-
PPRs. It has been demonstrated that the likelihood of find- tially provocative and thus need to be administered with the
ing a PPR is more or less equal with dim surrounding lights utmost care. Several patients do not like to be subjected to
and darkness (Van Egmond et al., 1980). Only in patients IPS, especially after bad previous experiences such as an
with suspected fixation-off and scotosensitive epilepsy, IPS-evoked generalized seizure. To gain confidence, it is
additional registration in darkness is useful as well (Pana- very helpful to explain the stimulation procedure, that is,
yiotopoulos, 1998). threshold stimulations and the cessation of stimulation as
Epilepsia, 53(1):16–24, 2012

doi: 10.1111/j.1528-1167.2011.03319.x
19
soon as generalized epileptiform discharges are seen in the A. Stop the visual stimulus immediately as soon as general-
EEG. ized epileptiform discharges occur during any flash fre-
quency, regardless of whether the discharges stop at the end
J. Instruct the patient to look at the center of the lamp and to
of the stimulus or continue after that (i.e., they are self-sus-
close their eyes when asked.
taining).
Comment: Stimulation of the central part of the retina is
Comment: Although some older studies (Reilly & Peters,
most effective in provoking a PPR (Wilkins et al., 1980).
1973) have suggested that only self-sustaining PPRs are
Eye closure on command, especially at the onset of the train
associated with epilepsy and seizures, later studies have
of flashes, is most provocative. Eye closure not only sets the
shown that also non–self-sustaining generalized discharges
brain in a more excitable state (as seen in normal records in
can have the same impact (Puglia et al., 1992; Nagarajan
the alpha squeak phenomenon), but also provokes a diffu-
et al., 2003). Waiting for self-sustaining PPRs is thus not
sion of light over the entire retina. Flashing during the eyes-
appropriate.
open condition is the least effective in evoking a PPR
(Kasteleijn-Nolst Trenit, 1989). The red filter effect of the B. Determine IPS sensitivity in three eye conditions with
eyelids probably plays a role in this. Stimulation with a dif- separate trains of flashes of 5 s duration each during eye clo-
fuser (a translucent paper in front of the patient’s eyes) has sure, eyes closed, and eyes open.
been proposed as a highly efficient technique in simulating
If there is not enough time, choose the eye closure condition
the eye closure and eyes closed condition (Leijten et al.,
(closure of the eyes on command at the start of a flash train)
1998). It can be very useful in noncooperative patients, but
and stimulate for 7 s per flash frequency
has the disadvantage that the face is no longer visible.
Infants are usually attracted by flashing light and look Comment: Eye closure is by far the most provocative eye
into the lamp; otherwise the child’s attention could be condition. Ten percent of photosensitive patients are detec-
attracted by holding a toy behind and above the lamp. ted exclusively with performance of eye closure during IPS
In children <4 years of age, or with conditions that limit (Kasteleijn-Nolst Trenit, 1989). Children older than 4 years
cooperation (i.e., intellectual disability, behavioural distur- of age are usually capable of performing eye closure.
bances, and so on), eyes can be kept closed by the parent or If recording time is limited, choose eye closure only and
by the technician. expand the flash duration to 7 s. In doing so eye closure is
partly combined with eyes closed with diminishment of the
IPS procedure on the basic level total duration of IPS to 2 min max, in case there is no PPR at
The purpose is to gather as much information as possible any flashfrequency. The disadvantage is that, both condi-
and in a concise way for clinical purposes; it is not a goal to tions are hard to disentangle.
lower the epilepsy threshold but simply to assess whether To know whether patients react to IPS during eye closure
there is a susceptibility to visual stimuli in daily life. is relevant, because these will occur during the watching of
Confirmation and exclusion of photosensitivity are equally TV or in sunshine, and so on. See Fig. 1 as an example of
important. IPS during eye closure on demand.
Figure 1.
IPS at 8 Hz during eye closure on
demand evokes a generalized
photoparoxysmal response in a
23-year-old woman with twice-daily
50 mg lamotrigine. EEG registration
was performed at 30 mm/s with
sensitivity 10 lV, high frequency
filter 70 Hz, and low frequency
filter 0.3 s.
Epilepsia ILAE
Epilepsia, 53(1):16–24, 2012

doi: 10.1111/j.1528-1167.2011.03319.x
20
C. Use the following flash frequencies separately and in this 70 patients (age range 13–73; average 31 years) with a
order: 1 – 2 – 8 – 10 – 15 – 18 – 20 – 25 – 40 – 50 – 60 Hz. generalized PPR in one or more eye conditions (personal
If there is a generalized response at a certain frequency data DKNT).
(lower threshold), skip the remainder of the series and start In most laboratories, traditionally a mix of even and
again with 60 Hz and go down in frequencies (60 – 50 – 40 uneven frequencies are given; although no controlled trials
– 25 Hz- …) until again a generalized PPR occurs (upper or published peer-reviewed data are available, patients
threshold). When in doubt if a particular frequency has pro- appear to react stronger to even than odd frequencies. Rep-
voked a generalized PPR, repeat the frequency after a rest of etition of the same frequency within a time frame of sec-
10 s or give a frequency of 1 Hz difference. onds might change the type of response (silent period;
Forster et al., 1964). One can thus take another close flash
Comment: The low frequencies of 1 and 2 Hz are for
frequency or wait longer before repeating the same fre-
detection of progressive myoclonic epilepsies (Rubboli et al.,
quency.
1999). The patients who are sensitive specifically to the
See Table 1 as an example; the emptied form can be used
higher frequencies are more sensitive to fluorescent lighting
for clinical purposes also.
and TV. Most patients are sensitive between 10 and 30 Hz
(Harding & Jeavons, 1994). In order to prevent seizure D. Observe clinical signs during the PPRs and ask the
occurrence, lower and upper thresholds of sensitivity are patient about any complaints he/she might have felt.
determined as described earlier.
Comment: Clinical signs and symptoms give valuable
The number of flash frequencies is diminished by 5 (five
information about the type of seizures and epilepsy the
times 30 s per flash frequency, all eye conditions included =
patient has and allow correlation with clinical history data
150 s; 30%) compared to the first methodology proposal of
(Trenit, 2006). Patients can be taught to recognize their
2001 in order to shorten the IPS recording time. The current
signs and symptoms during epileptiform EEG activity and
proposal takes 5 min of IPS at maximum (5 s IPS and 5 s
use them to prevent seizures induced by visual stimuli in
rest times three eye conditions = 330 s) when the patient is
daily life.
either not sensitive or sensitive to only one frequency; in this
case all frequencies are done only once and when arriving at
IPS procedure on a higher level of sophistication
60 Hz the stimulation can be stopped. Otherwise, the dura-
The purpose is to gather as much information as possible
tion will be shorter; the more sensitive a patient, the less
for clinical and research purposes. Thanks to a greater range
time it will take, because stimulation stops at the lower and
of visual stimuli tested like pattern and videogames etc., a
upper threshold frequencies (Kasteleijn-Nolst Trenit et al.,
more precise individualized advice about potential provoca-
1999a,b). If a patient shows a generalized PPR at, for exam-
tive visual stimuli and therapeutic measures can be given.
ple, 8 Hz (lower threshold) and at 40 Hz (upper threshold),
the total number of stimulations has been six frequencies A. Use electrodes for recording eye movements and surface
with a total duration of stimulation of 3 min (six times axial electromyography (EMG) recording to detect subtle
30 = 180 s). myoclonus
By following this strategy a sensitivity range can be
Comment: Eye movement recording permits more pre-
determined that is individual, is related to the liability to sei-
cise registration and, therefore, discrimination between the
zures in daily life, and changes with age and use of AEDs.
different eye conditions and especially the detection of
If only 18 Hz is used, about 15% of patients will not be
self induction with slow eye closures (Kamp & Lopes da
detected as being photosensitive because they are sensitive
Silva, 1987). For detection and more precise registration of
at other frequencies, as has been seen in a population of
Table 1. Scoring table photic stimulation

Name: A. K.
Date of birth: 20-12-1992 Date: 7-5-2011
Medication: none Time: 9.30
Flash frequency (Hz) 1 2 8 10 15 18 20 25 40 50 60
Eye condition
Eye closure ) ) + 0 0 0 0 0 + ) )
Eyes closed ) ) ± ± + 0 + ± ) ) )
Eyes open ) ) ) ) ± + ± ) ) ) )
In this scoring table, an example is given of determination of the three photosensitivity ranges based on the proposed methodology.
Photosensitivity ranges eye closure: 8–40 Hz; eyes closed: 15–20 Hz; eyes open: 18 Hz. Explanation of codes + : generalized epileptiform discharges; ±: epileptiform
discharges, not generalized; ): no epileptiform discharges; 0: frequency not tested.
Epilepsia, 53(1):16–24, 2012

doi: 10.1111/j.1528-1167.2011.03319.x
21
clinical events, including negative myoclonus (Rubboli 300 cd/m in a well-lit room or on an LCD monitor with a
et al., 2004), EMG is helpful. steady backlight. Patterns of increasing size are presented in
succession having radii of 3, 6, 12, and 24 degrees, and the
B. Test IPS sensitivity in three separate eye conditions (eye
series is terminated if a PPR occurs. In one series the stripes
closure, eyes closed, and eyes open).
are black and white and in a second series they are red and
Comment: Eye closure is the most provocative condition. blue.
Ten percent of photosensitive patients are detected only
Comment: Potentially epileptogenic visual stimuli are
with performance of eye closure during IPS (Kasteleijn-
commonplace in the modern urban environment. They
Nolst Trenit, 1989). Eye closure at the start of the stimulus
include not only geometric patterns, but also to a lesser
train of 5 s duration is different from the eyes closed condi-
extent more complex designs, even works of modern art.
tion; after eye closure an alpha squeak (Storm van Leeuwen
It is important to know whether a patient is likely to be sen-
& Bekkering, 1958) occurs and the threshold for a PPR sub-
sitive to visual stimuli that do not flicker. In nature, images
sequently diminishes. The duration of the flash-train can be
have a particular power spectrum in which the luminous
longer if thought useful, for example, if there is a history of
contrast energy decreases with increasing spatial frequency
juvenile myoclonic epilepsy or video game seizures (Apple-
as the reciprocal of the frequency, that is, a graph of log con-
ton et al., 2000; Waltz & Stephani, 2000).
trast energy against log spatial frequency is linear with a
C. Use the following flash frequencies in this order: 1 – 2 – 6 slope of about )1. Images in which the power spectrum
– 8 – 9 – 10 – 13 – 15 – 18 – 20 – 23 – 25 – 30 – 40 – 50 – departs from this simple relationship are uncomfortable to
60 Hz. If there is a generalized response at a certain fre- view (Juricevic et al., 2010). Those images with an excess
quency, skip the remainder of the series and continue then of contrast energy at mid-range spatial frequencies relative
with 60 Hz and go down in frequencies (60 – 50 – 40 – 30 – to the energy expected are particularly uncomfortable (Fer-
25 Hz- …) until again a PPR occurs. nandez & Wilkins, 2008). If an image has all its energy at
mid-range spatial frequencies, it is not only uncomfortable
Comment: Retesting of photosensitive patients gives the
but is also epileptogenic. This can be examined in the labo-
opportunity to determine more precisely the photosensitivi-
ratory using nonflickering patterns with the above-men-
ty range.
tioned parameters. The purpose of increasing the radius is to
D. Stimulation with colored flashes in patients with a history determine thresholds for evaluation of drug effects and age
of TV and videogame epilepsy. as well as to reduce the risk for seizures.
Comment: Since the Pokmon incident in Japan (Furusho F. Video games and cartoons on TV and computer screens.
et al., 2002), much attention has been given to color stimu-
Comment: When patients have a history of seizures or
lation emitted through the TV. Color stimulation can be a
complaints while playing or viewing a specific video game
powerful tool to trigger PPRs at a low-luminance level that
or cartoon, ideally these are presented in the laboratory with
may be especially prominent in a subset of patients. It is per-
concurrent video-EEG recording.
formed only in the eyes-open condition with a luminance of
Testing different TV sets in the EEG lab would provide
20–30 cd/m2, and it is especially effective at frequencies of
the patient and family with a good understanding of one of
<30 Hz, as the stimulation is conveyed mainly by the parvo-
the most provocative settings that might trigger seizures in
cellular pathway (Takahashi et al., 1999; Parra et al., 2007).
the home environment and learn techniques to avoid the risk
Red light of wavelength >600 nm seems to be particularly
of seizures. This test would be available in only a few EEG
effective, and it has been argued that this is because it over-
labs dedicated to this specific field. Several minutes of
comes the antagonistic effects of cone stimulation by pro-
recording may be necessary to elicit PPR in this situation.
viding maximal stimulation to the occipital cortex (Binnie
The new developments in the field of television screens
et al., 1984). Alternating red and blue stimulation seems to
including three-dimensional (3D) devices as well as the
be an even more provocative stimulus, with a synergistic
increasing popularity of video games among youth (the seg-
effect not predictable by the sensitivity to red or blue light
ment of the population most sensitive to seizures triggered
alone (Parra et al., 2007). Young teenagers seem to be par-
by visual stimuli) will warrant more research oriented to the
ticularly at risk from these stimuli (Yamasaki et al., 2008).
properties of these devices and the peculiarities of the stim-
Alternating stimulation with colors far apart in color space
uli they will be able to convey. Although some specific
might also be very effective in triggering PPRs (Wilkins
research will undoubtedly be centered in specific programs
et al., 2008).
with an unusual power to trigger seizures (like the Pokmon
E. Stimulation with black-and-white evenly striped patterns episode or the footage of the London Olympic games), we
(gratings that are circular in outline and centrally fixated) believe that the analysis of these programs and video game-
with spatial frequency between 2 and 4 cycles per degree, scenes should be done from the perspective of the
Michelson contrast >0.8, and a mean luminance of at least fundamental properties of the visual system rather than
Epilepsia, 53(1):16–24, 2012

doi: 10.1111/j.1528-1167.2011.03319.x
22
focusing on individual properties of the image itself. Cur- as triggering different types of PPR: excitation of the
rently commercial devices like the Graham Harding pattern parvocellular system by colored stimuli would be more
analyzer of Cambridge Research can analyze video epileptogenic, eliciting a generalized PPR, whereas stim-
sequences and detect those segments with features able to ulation of the magnocellular system would result in a
trigger seizures (See http://www.hardingfpa.com). milder PPR, represented by occipital spikes (Harding &
Fylan, 1999). Moreover, it has been recently demon-
G. Observe clinical signs with precision during the PPRs
strated that color sensitivity depends on two mechanisms:
and ask the patient about any complaints he/she might have
one related to color modulation, intervening at low fre-
felt (Note: Recording of eye movement/myoclonus or of
quencies, and the other dependent on single-color light
axial myoclonus is fundamental.)
intensity modulation and related to white light sensitivity
Comment: Clinical signs and symptoms provide valuable that is activated at higher frequencies (Parra et al., 2007).
information about the type of seizures and epilepsy the Further research in this field, by using different tech-
patient has and allows correlation with clinical history data. niques [i.e., magnetoencephalography (MEG), visual
The clinical signs and symptoms might be different for evoked potentials, functional imaging, optical imaging]
the various types of stimuli, being focal or generalized, (Parra et al., 2003; Schwartz, 2003) to deepen the com-
although in most cases the signs will be similar (Piccioli prehension of the different pathophysiologic mechanisms
et al., 2005). Headache can even be the only symptom dur- of photosensitivity, may provide the information neces-
ing a PPR, and EEG recording with photic stimulation as sary to develop more effective therapeutic measures
described above helps in discriminating between migraine (drugs, protective lenses) and to define more precisely
and epilepsy (Parisi, 2009; Kasteleijn-Nolst Trenit et al., endophenotypes for genetic research.
2010). Patients can be taught to recognize this feeling and Application of specific types of visual-evoked poten-
use it for prevention of seizures induced by visual stimuli in tials, using special parameters, might contribute to further
daily life. clarify the role of the parvo and magno systems in gener-
ating abnormal visually driven cortical responses
(Porciatti et al., 2000) and to define which are the poten-
Future Developments tially dangerous regions of the visual spectrum, in order to
Future developments in the study of photosensitivity design safer visual stimuli by eliminating hyperactivating
should address three main issues: features of the visual information, and eventually to test
1 Definition and standardization of methodologic proce- the protective effects of drugs. Investigation of visual
dures to reliably detect photosensitivity either in the labo- habituation in photosensitive patients may permit the
ratory or in environmental conditions. Indeed, at present, identification of imbalances in excitatory and inhibitory
no known method is recognized as able to fully determine cortical processes mediating the abnormal responses to
the risks of visually induced seizure precipitation in a visual stimuli, which may reflect impaired neurotransmis-
highly susceptible person, although proposals for stan- sion (Shepherd & Siniatchkin, 2009; Brazzo et al., 2011).
dardized procedures have been made (Kasteleijn-Nolst Finally, research on photosensitivity should take also
Trenit et al., 1999a,b). Indeed, additional methodologic into account that photosensitive epilepsy, as the most
studies on standardization of IPS are still necessary to common form of reflex epilepsy (i.e., epilepsy in which
demonstrate the yields provided by using adequate equip- epileptic manifestations can be triggered by external
ment and appropriate procedures to reliably detect photo- factors), represents a privileged model to investigate in a
sensitivity (Rubboli et al., 2004; Specchio et al., 2010). controlled fashion the brain processes that intervene in
Development and implementation of visual evoked the transition from the interictal to the ictal state, opening
potential recordings may also be useful for identifying a window on the mechanisms of ictogenesis and, possi-
abnormal susceptibility to light stimuli by using nonpro- bly, epileptogenesis.
vocative visual stimulation (Vermeulen et al., 2008). 3 Development and implementation of preventive mea-
Finally, the clear definition of the phenotype Epilepsy sures and guidelines. Development and implementation
with Photosensitivity identified by the methodologies of guidelines to minimize exposure of susceptible
described here will refine the cohorts of patients involved populations to provocative stimuli are an important
in genetic and other research (Trenit, 2006). public health issue. In fact, the Pokmon incident in
2 Elucidation of the pathophysiologic mechanisms underly- Japan stimulated a debate on the need for regulations
ing photosensitivity. Present knowledge on pathophysiol- and protective measures for video material, particu-
ogy of epileptic photosensitivity points to two types of larly for television programs, to prevent seizure pre-
mechanisms—mediated by the magnocellular and parvo- cipitation. Since then, guidelines have been indeed
cellular systems—that contribute either synergistically or implemented in the UK and in Japan; however, an
independently to elicit a PPR. Selective activation of par- agreement on the application of global homogeneous
vocellular or magnocellular divisions has been proposed guidelines has not yet been achieved. Updated
Epilepsia, 53(1):16–24, 2012
doi: 10.1111/j.1528-1167.2011.03319.x
23
guidelines and recommendations should consider the role Kasteleijn-Nolst Trenit DGA, Binnie CD, Meinardi H. (1987) Photosensi-
tive patients: symptoms and signs during intermittent photic stimulation
of parameters such as modulation depth and stimulus and their relation to seizures in daily life. J Neurol Neurosurg Psychia-
wavelength at provocative frequencies and the increasing try 50:1546–1549.
availability of modern audiovisual technology that Kasteleijn-Nolst Trenit DG. (1989) Photosensitivity in epilepsy: electro-
physiological and clinical correlates. Acta Neurol Scand 125(Suppl.):
employs large screen without flicker effects but with sig- 3–149.
nificant changes of other variables (for instance, lumi- Kasteleijn-Nolst Trenit DGA, Binnie CD, Harding GFA, Wilkins A.
nance of the screen and the separate stimulation of the (1999a) Photic stimulation: standardization of screening methods.
Epilepsia 40:75–79.
two eyes). To pursue this goal, sensitization and coopera- Kasteleijn-Nolst Trenit DGA, Binnie CD, Harding GFA, Wilkins A, Cov-
tion from the industry are necessary as well as the anis T, Eeg-Olofsson O, Goosens L, Henriksen O, Krmer G, Leyten F,
involvement of broadcasters and producers. Lopes da silva FH, Martins da Silva A, Naquet R, Pedersen B, Ricci S,
Rubboli G, Spekreijse H, Waltz S. (1999b) Medical technology assess-
ment, photic stimulation – standardization of screening methods. Neu-
Acknowledgments rophysiol Clin 29:318–324.
Kasteleijn-Nolst Trenit DGA, Guerrini R, Binnie CD, Genton P. (2001)
Visual sensitivity and epilepsy: a proposed terminology and classifica-
DKNT has been supported by the European Marie Curie Excellence
tion for clinical and EEG phenomenology. Epilepsia 42:692–701.
Grant ‘‘Visual sensitivity’’ (FP6 European research program, # 024224).
Kasteleijn-Nolst Trenit DG, Verrotti A, Di Fonzo A, Cantonetti L, Bruschi
R, Chiarelli F, Villa MP, Parisi P. (2010) Headache, epilepsy and
photosensitivity: how are they connected? J Headache Pain 11:469–
Disclosure 476.
Kasteleijn-Nolst Trenit DGA, Waltz S, Rubboli G. (2011) Photosensitivity
None of the authors has any conflict of interest to disclose. We confirm and syndromes. In Genton P, Bureau M, Dravet C, Thomas P, Delgado-
that we have read the Journal’s position on issues involved in ethical publi- Escueta A (Eds). Epilepsy syndromes in infancy, childhood and
cation and affirm that this report is consistent with those guidelines. adolescence, 5th ed. John Libbey Eurotext, Montrouge, France,
pp. 666–999, in press.
Labate A, Ambrosio R, Gambardella A, Sturniolo M, Pucci F, Quattrone A.
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Epilepsia, 53(1):16–24, 2012

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(2012) - Methodology of Photic Stimulation Revisited Updated European Algorithm For Visual Stimulation in The EEG Laboratory

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CRITICAL REVIEW AND INVITED COMMENTARY

Methodology of photic stimulation revisited: Updated

stantially increased content, detailing technical and logisti-

Why Photic Stimulation? (repeatedly) be gathered, for example, in diagnosing syn-

Epilepsia, 53(1):16–24, 2012

Epilepsia, 53(1):16–24, 2012

Epilepsia, 53(1):16–24, 2012

Table 1. Scoring table photic stimulation

Epilepsia, 53(1):16–24, 2012

Epilepsia, 53(1):16–24, 2012

Epilepsia, 53(1):16–24, 2012

Epilepsia, 53(1):16–24, 2012

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